Thursday, June 30, 2011

HIV disrupts blood-brain barrier

HIV weakens the blood-brain barrier — a network of blood vessels that keeps potentially harmful chemicals and toxins out of the brain — by overtaking a small group of supporting brain cells, according to a new study in the June 29 issue of The Journal of Neuroscience. The findings may help explain why some people living with HIV experience neurological complications, despite the benefits of modern drug regimens that keep them living longer.

Standard antiretroviral treatments successfully suppress the replication of HIV and slow the progression of the disease. Yet recent studies show 40 to 60 percent of patients on such therapy continue to experience mild to moderate neurological deficits — including memory loss and learning challenges.

In the new study, Eliseo Eugenin, PhD, of Albert Einstein College of Medicine, found that HIV infection in a small number of supporting brain cells called astrocytes breaks down the blood-brain barrier, despite low to undetectable viral production. Under normal conditions astrocytes help bolster the blood vessels comprising the barrier.

Astrocytes (pictured in green) help to support blood vessels (red) that act as the blood-brain barrier - a network that keeps potentially harmful chemicals and toxins out of the brain. This image shows the close interaction between the cells in the human brain. Credit: Eugenin, et al. The Journal of Neuroscience 2011.

To test if HIV interfered with this support system, Eugenin and his colleagues built a model of the blood-brain barrier using human cells in the laboratory. In a previous study, the researchers found HIV infects around 5 percent of astrocytes. In the current study, the researchers found the presence of HIV in a similar percentage of astrocytes led to the death of nearby uninfected cells and made the barrier more permeable.

As the neighboring cells died, however, HIV-infected astrocytes survived. Astrocytes exchange chemical signals through specialized molecules called gap junctions. When they were blocked in the model, it prevented the changes to the blood-brain barrier and nearby cells, suggesting the infected astrocytes relay toxic signals to neighboring cells through the gap junctions.

“Our results suggest HIV infection of astrocytes may be important in the onset of cognitive impairment in people living with the disease,” Eugenin said. “New therapies are needed that not only target the virus, but also to stop the virus from spreading damage to other uninfected brain cells.”

Eugenin’s group also analyzed the brain tissue of macaque monkeys infected with the simian form of HIV. Similar to what they saw in the human blood-brain barrier model, the researchers found uninfected cells in contact with HIV-infected astrocytes died, while infected astrocytes remained alive as the disease progressed.

“Researchers have been stymied to explain why HIV-associated neurological complications persist, despite potent combination antiviral therapies that have dramatically improved health and survival,” said Igor Grant, an expert who studies HIV-associated neurocognitive impairment at the University of California, San Diego. “This study provides a possible explanation indicating that minute numbers of infected astrocytes can trigger a cascade of signals that could open the brain to various toxic influences.”

The findings open up the possibility of developing new therapeutic approaches that block or modify the transmission of signals from the HIV-infected astrocytes, added Grant, who was not affiliated with the study.

Gilead Sciences has announced a new alliance with Tibotec Pharmaceuticals that will see the companies produce a combination treatment for HIV.

The license agreement will focus on the development and commercialisation of a fixed-dose antiretroviral therapy, combining Tibotec's approved HIV drug Prezista with Gilead's investigational pharmacoenhancing agent cobicistat.

Should this treatment be approved, Tibotec would take responsibility for its global production and sales, with Gilead retaining the rights to cobicistat as a standalone product.

The companies are also in discussions over a similar collaboration to create a single-tablet HIV regimen combining Prezista with Gilead's compounds Emtriva and GS 7340, as well as cobicistat.

Dr Norbert Bischofberger, Gilead's executive vice-president for research and development and chief scientific officer, said: "This agreement represents another important step forward in our commitment to developing simplified treatment regimens that can help address the individual needs of people living with HIV."

Earlier this year, the company entered into an alliance with MicroDose Therapeutx to develop a new treatment for respiratory syncytial virus.

Wednesday, June 29, 2011

If you’re HIV positive, safe sex isn’t just about condomsDeborah Jack

As the HIV epidemic has evolved over three decades, the “just use a condom” message has remained the cornerstone of prevention. But stubbornly high levels of new HIV infections in the UK show we’ve struggled to always translate this simple message into real life.

Most monogamous couples will decide to stop using condoms at some point, but what if one half of the couple is HIV positive? Until recently, it has been assumed there is no safe option other than condoms for life. But new research into the preventive benefits of HIV treatment (antiretroviral therapy) is set to change this, and could potentially revolutionise the way we think about HIV prevention and safer sex advice.

HIV treatment works by reducing the level of HIV in the body (the viral load) to such an extent that a person’s infectiousness is almost zero (clinically referred to as “undetectable”). A big effect of this — in addition to keeping the person healthy — is that the risk of transmitting HIV to another person is dramatically reduced.

Last month we heard the conclusive results of the first global study into HIV “treatment as prevention” — a 96% reduction in transmission risk when the HIV-positive partner received treatment and responded effectively. When put into practice, this means people living with HIV who are on treatment can, like everyone else, consider giving up condoms when their relationship is committed and monogamous.

But before we get carried away, it is not time to throw away our condoms altogether. They are still the best protection against other sexually transmitted infections, so any couple wanting to rely on treatment rather than condoms to prevent HIV transmission must be confident they are both STI free and monogamous. Other STIs in the body can make HIV levels spike upwards, which seriously compromises the effects of treatment as prevention and significantly increases risk of transmission.

The notion of ditching the condoms when one half of a couple is HIV positive also throws up other practical challenges in a relationship. A condom is visible, its use is mutual, and if it fails this is usually evident. By contrast, the level of HIV in a person’s body is invisible has been measured at some point in the past (up to four months, usually) and that information has been given to only one of the sexual partners. Very different issues of trust are involved and to rely on this method means relying in both partners’ faithfulness, or on their courage to come clean if they have sex with anyone else.

Last year, at the National Aids Trust’s seminar on HIV treatment as prevention, we heard stories from couples who were in this situation and trying to navigate their safer sex options in a way that suited them both.

Some couples were happy to rely on treatment as prevention, but for others it was a lot more complex. In some instances the negative partner was happy to rely on treatment but the positive partner was too worried about the risk (however small) of passing HIV on to the one they love. For others it was the opposite, with the HIV-negative partner anxious about risk of infection despite the HIV positive partner’s desire to no longer use condoms.

What is clear from people’s experiences is that HIV treatment as prevention is not some “quick fix”. There remain complex issues of love and trust to negotiate, as well as unlearning the internalised stigma and fear around HIV, which people have lived with for years.

This is not to say that treatment as prevention will only have benefits for those who are in long-term, monogamous relationships. Being on treatment will still reduce infectiousness even if you have more than one partner, but you could not rely on it to prevent transmission in the same way that an exclusive couple might.

Additionally, one of the biggest barriers to HIV treatment as prevention is the fact that at least a quarter of people living with HIV in the UK have not been diagnosed — and therefore are not on treatment.

So with the exception of those in completely monogamous (and honest) relationships, the message is still “use condoms”. But the fact remains that people will always make their own decisions based on the level of risk they’re prepared to live with.

What we need is clear guidance on how individuals should be advised on using “treatment as prevention” as a safer sex option and this should be combined with renewed efforts to encourage condom use. Crucially, this will require appropriate, accessible support for those people who find using condoms or negotiating their use difficult — a much larger number of people than is usually acknowledged.

Thirty years into the epidemic, an HIV prevention revolution could be upon us. But the basic need for well-resourced, appropriate HIV and sexual health support services remains the same. And while we aren’t ready to lay condoms to rest just yet, the “just use a condom” message can now be combined with a new source of encouragement for those diagnosed with HIV that if they commence and stick to their treatment, when the timing is right in their lives there will be another option available to them for safer sex.

Tuesday, June 28, 2011

A 51-year-old woman with HIV presented with weight gain and a 1-month history of right hip pain. Her ART included tenofovir (300 mg once daily), emtricitabine (200 mg once daily), and atazanavir/ritonavir (300/100 mg once daily). Because of previous bilateral cytomegalovirus retinitis, complicated by immune recovery uveitis with severe, chronic, cystoid macular oedema, she was also using dexamethasone 0.1% eye drops six times daily, and betamethasone 0.1% eye ointment at night, in both eyes.

On examination, she was noted to have central adiposity and enlargement of the dorsocervical fat, but no peripheral lipoatrophy. An MRI scan of the hip showed avascular necrosis. A tetracosactide (Synacthen) stimulation test showed marked suppression of the pituitary-adrenal axis, with a baseline cortisol of less than 25 nmol/L rising to only 37 nmol/l 30 min after administration of tetracosactide 250mg (normal response at 30 min, >570 nmol/L). Adrenocorticotropic hormone (ACTH) was undetectable.

The presence of adrenal axis suppression with low ACTH, in the context of Cushingoid features and avascular necrosis of the hip, suggested ongoing exposure to high systemic levels of exogenous corticosteroids. Ritonavir and atazanavir were substituted with efavirenz (600 mg once daily), while continuing the steroid eye drops. Oral hydrocortisone 15 mg daily was added to avoid precipitating crisis due to adrenal insufficiency. Over the following year, the patient’s weight declined, with marked improvement in her adrenal function. Analysis of stored serum samples revealed elevated levels of dexamethasone at presentation (1.4-1.7 nmol/L) which fell dramatically after discontinuation of protease inhibitor therapy (undetectable to 0.181 nmol/L).

Although prior courses of oral and intravenous corticosteroids may have contributed to adrenal axis suppression, the close temporal correlation between discontinuation of ritonavir, reversal of weight gain and recovery of adrenal function, combined with detectable levels of dexamethasone in the blood, strongly suggests that co-administration of ritonavir was responsible for the accumulation of excessive systemic levels of topical ocular corticosteroids, resulting in adrenal axis suppression and Cushing’s syndrome.

Tibotec Therapeutics—the research and development division of Janssen Pharmaceuticals—has entered an agreement with Gilead Sciences to develop a fixed-dose combination (FDC) tablet containing its protease inhibitor Prezista (darunavir) and Gilead Sciences’ experimental boosting agent cobicistat, according to a Janssen announcement.

During the past decade, a number of different HIV drugs have been combined into single pills, both to reduce the total number of pills that people with HIV take and to extend the rights of companies to exclusively sell their drugs. The most successful of these combinations, Atripla—which contains Bristol-Myers Squibb’s Sustiva (efavirenz) and Gilead’s Truvada (tenofovir plus emtricitabine)—was the first to combine drugs from two different companies.

Aside from Kaletra, which combines Abbott Laboratories’ lopinavir and ritonavir, there are no other protease inhibitors (PIs) co-formulated with other necessary agents designed to minimize dosing requirements while at the same time boosting effectiveness. With Gilead developing an agent, cobicistat, that can be used as an alternative to Norvir (ritonavir) to boost blood levels of other PIs, some PI manufacturers have expressed interest in partnering with Gilead to develop co-formulated products that can further minimize daily pill counts.

“We are excited to be able to study and develop Prezista with an alternative boosting agent in a combination product which has the potential to reduce the number of tablets patients take,” said Johan Van Hoof, MD, of Janssen. “Prezista is one of the leading protease inhibitors, and co-formulating it with cobicistat in a new combination product demonstrates our commitment to HIV and innovations that will provide new options for patients.”

The deal to combine Prezista with cobicistat will depend on two criteria. First, the U.S. Food and Drug Administration (FDA) must approve cobicistat. This approval is anticipated sometime within the next year. The second, according to Janssen, is that negotiations between it and Gilead on another FDC tablet must also be complete.

This other FDC will combine Prezista and cobicistat with Gilead’s Emtriva (emtricitabine) and another Gilead drug that is in early stage testing. That drug, GS-7340, requires much lower doses than Viread and is expected to remain in the body for a long time before it is eliminated. This would make it ideal to combine with other drugs.

Janssen said it will have full rights and responsibilities for manufacturing and marketing the FDC of Prezista and cobicistat, while Gilead will take full responsibility for manufacturing and marketing the FDC of four drugs

HIV can hide out in the brain, protected from the immune system and antiviral drugs, Dr Lachlan Gray and his colleagues at Monash University and the Burnet Institute have found.

Their discovery is an important step in understanding the link between HIV infection and HIV dementia, and is important for the eradication of HIV in general.

“The persistence of the virus in the brain compromises the brain’s normal function, and leads to the death of neurons and to clinical dementia,” Lachlan says.

In fact, about one in five of those infected by HIV ends up with dementia.

“We believe our findings will aid the development of novel drugs that will prevent HIV using the brain as a sanctuary, and help to shape future eradication strategies.”

Lachlan’s work is being presented for the first time in public through Fresh Science, a communication boot camp for early career scientists held at the Melbourne Museum. He was one of 16 winners from across Australia.

Lachlan has been examining the life cycle of the virus to understand better how it survives within the brain.

“We’ve identified changes in the way the virus reproduces, which allows it to keep a low profile and persist undetected in the brain.”

At present, people living with HIV must rely on the continued use of antiviral drugs to control their infection.

“Viral persistence is a major barrier to the cure of AIDS. Modern drugs are very good at controlling the virus, but they are unable to eradicate it from ‘sanctuary’ sites like the brain,” Lachlan’s supervisor, Associate Professor Melissa Churchill says.

“Unfortunately, brain infection often leads to dementia which can be very debilitating. Somewhat more concerning, HIV is now the commonest cause of dementia in people under the age of 40, and is placing an extra burden on our mental health services.”

Lachlan’s research is part of a larger project aiming to trial new drugs that could potentially eradicate or even cure HIV.

Lachlan Gray is one of 16 early-career scientists unveiling their research to the public for the first time thanks to Fresh Science, a national program sponsored by the Australian Government.

His challenges included presenting his discoveries in verse at a Melbourne pub.

Monday, June 27, 2011

Lessons from maraviroc clinical trials

Maraviroc is the first commercially available HIV chemokine receptor antagonist targeting HIV that utilizes the CCR5 chemokine receptor (R5 tropic). The Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) trials were two randomized, placebo-controlled studies designed to demonstrate the activity of maraviroc in triple-class-experienced HIV individuals, with a primary end point of viral load suppression at 48 weeks. Maraviroc outperformed the placebo plus optimized background (OBT) arm, and exhibited a favorable safety profile with low discontinuation rates, which equaled those of the placebo plus OBT group. The results of these trials led to maraviroc receiving regulatory approval for the treatment of HIV.

The Food and Drug Administration (FDA) has recommended the use of Pfizer's Selzentry as an initial treatment for HIV patients, despite continuing concerns over the level of effectiveness of the drug.

Selzentry had been approved earlier as a secondary drug for HIV-infected people who do not benefit from other antiviral treatments. But Pfizer had been seeking its use on patients who were not already under treatment to fight HIV.

In initial studies where it was compared with Sustiva, an antiviral manufactured by Bristol-Myers Squibb, Selzentry failed to prove it was at least as effective.

Of the patients who were tested, 32% given Selzentry did not show a sufficiently effective response, against 24% for Sustiva.

However, after Pfizer repeated the trials using a different method to screen participants it was able to meet the target.

Experts on the FDA panel, while voting 10-4 in favour of approving the drug as a first option for HIV patients, also raised concerns about its effectiveness.

Dr Russell Van Dyke of the Tulane University School of Medicine, said: "It's clearly an active drug, it demonstrated effectiveness. But I'm worried it's not as potent as we might like."

Saturday, June 25, 2011

Selzentry is designed to prevent R5-tropic HIV from entering your T-cells

SELZENTRY was specially designed to target R5 HIV, a common type of HIV. To find out if you have R5 HIV, you can be prescreened with an HIV tropism test (sometimes called a tropism assay). This can let you see right away if SELZENTRY could be part of your personalized HIV therapy program.

A tropism test is a blood test that reveals how your HIV enters T-cells. HIV can enter T-cells via an R5 or X4 co-receptor. A tropism test reveals which of these receptors your HIV uses.

You have R5-tropic HIV if HIV uses the R5 co-receptors to enter your T-cells. You have X4-tropic HIV if HIV uses the X4 co-receptors to enter your T-cells. You have dual or mixed tropic HIV if HIV uses both the R5 and the X4 co-receptors to enter your T-cells.

SELZENTRY® (maraviroc) is a CCR5 inhibitor that is used with other HIV medicines to treat CCR5-tropic HIV. SELZENTRY is not recommended in patients with dual/mixed or CXCR4-tropic HIV. It is for adult patients with CCR5-tropic HIV only. A tropism test is needed before starting SELZENTRY. SELZENTRY does not cure HIV infection or AIDS and does not lower the risk of passing HIV to other people.

People taking SELZENTRY may still develop infections, including opportunistic infections or other conditions that happen with HIV infection. The long-term effects of SELZENTRY are not known at this time. It is very important that you stay under the care of your healthcare provider during treatment with SELZENTRY.

Tobira Therapeutics is recruiting for a Phase IIb study of its CCR5/CCR2 entry inhibitor cenicriviroc (TBR-652). It is hoped that cenicriviroc will not only offer people a new antiretroviral (ARV) option to keep HIV in check, but that it will also prove useful in reducing the cellular inflammation that scientists believe is behind a host of health problems.

Cenicriviroc is from a class of drugs that blocks the CCR5 coreceptor on CD4 cells, thus making them resistant to HIV infection. It is in the same class of drugs as Selzentry (maraviroc) but may be used once-daily instead of twice-daily.

Cenicriviroc also has another unique attribute. In addition to blocking the CCR5 coreceptor, it also blocks another coreceptor called CCR2, which is involved in inflammatory diseases such as rheumatoid arthritis. In recent years, researchers have shown that cellular inflammation, even in people whose HIV is well controlled by ARV therapy, may contribute to a number of health problems, including cardiovascular disease. It is hoped, though it will take time to prove this, that cenicriviroc will be a dual-purpose drug—fighting HIV directly while also reducing HIV-related inflammation.

According to Tobira press materials, the new study will pit cenicriviroc against Sustiva (efavirenz), both of them paired with Truvada (tenofovir plus emtricitabine). Tobira will be studying two doses of cenicriviroc, 100 milligrams (mg) and 200 mg once-daily.

“This study is based on the strength of the cenicriviroc Phase IIa proof of concept, pharmacokinetic and safety findings that were presented at key HIV/AIDS conferences and published in peer-reviewed journals,” said Melanie Thompson, MD, of the AIDS Research Consortium of Atlanta, and a lead investigator in the Phase IIb study. “The study will further explore cenicriviroc’s antiviral activity and safety as well as effects on immunologic and inflammatory biomarkers, including the effects of CCR2 receptor inhibition in HIV-1 infected patients.”

To learn more about the cenicriviroc study, visit the clinical trials database run by the National Institutes of Health (NIH).

Friday, June 24, 2011

GeoVax Labs Inc. (GOVX) Opens Third Site for HIV/AIDS Vaccine Testing

GeoVax Labs Inc., a biotechnology company in operation to create, develop and test innovative HIV/AIDS vaccines, today announced it has opened a third site for testing the therapeutic potential of its HIV/AIDS vaccine in conjunction with the AIDS Research Alliance, the nation’s only independent, nonprofit research institute dedicated to the search for a cure for AIDS.

The Los Angeles-based ARA will team up with two existing members of GeoVax’s clinical trial site team, the AIDS Research Consortium of Atlanta and the Alabama Vaccine Research Clinic at the University of Alabama at Birmingham.

The therapeutic trial marks the first trial designed to test GeoVax’s vaccine as a possible treatment for HIV. The upcoming clinical trial will test safety, vaccine-induced immune responses, and the ability of the vaccine to control viral replication in HIV-infected patients.

GeoVax said previous studies involving simian prototypes of the vaccine in infected non-human primates demonstrated the vaccine’s ability to control viral replication in the absence of anti-viral drugs.

“We are excited to expand our therapeutic trial team to include the AIDS Research Alliance,” Mark Newman, PhD, vice president of Research and Development at GeoVax stated in the press release. “They are a group with a mission that parallels that of GeoVax, developing a vaccine to prevent infection by HIV and developing better treatments for those who become infected.”

Dr. Stephen Brown, ARA’s medical director, said that the development of new products and approaches that springing from existing antiretroviral drugs regimens would represent a major breakthrough in AIDS research.

GeoVax’s vaccines are currently being tested in HIV-uninfected persons in a phase II clinical trial by the HIV Vaccine Trials Network (HVTN), which are funded by the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health.

Scientists have designed molecular inhibitors that could delay the onset of Alzheimer’s disease and prevent the sexual transmission of HIV.

The researchers say the inhibitors target specific proteins associated with Alzheimer’s disease and HIV to prevent them from forming amyloid fibres, the elongated chains of interlocking proteins that play a key role in more than two dozen degenerative and often fatal diseases.

“By studying the structures of two key proteins that form amyloids, we were able to identify the small chain of amino acids responsible for amyloid fibre formation and engineer a ‘molecular cap’ that attaches to the end of the fibres to inhibit their growth,” research leader David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, said.

“This research is an important first step toward the development of structure-based drugs designed against amyloid diseases,” Eisenberg, who is a UCLA professor of chemistry, biochemistry and biological chemistry and a member of the California NanoSystems Institute at UCLA, said.

“Our results have opened up an avenue so that universities and industry can start creating therapeutics that could not have been produced 10 years ago,” he stated.

Eisenberg and his research team found that of the entire tau protein, a small chain of just six amino acids - abbreviated VQIVYK — was responsible for the formation of amyloid fibres.

By studying the structure of the fibres using microcrystallography, a method developed at UCLA for this research, the team was able to use the fibres as a template to design an inhibitor that could “cap” the fibre and stop it from growing.

The introduction of the inhibitor into a tau protein solution completely prevented amyloid fibre formation, validating the idea that the structure-based design of therapeutics for amyloid diseases is a plausible option.

The study has been published online June 15 in the journal Nature and will be available in an upcoming print edition.

MUMBAI: The clever HIV virus could be present in drastically different variants in the bodily fluids — blood and semen — of the same individual. This was recently established by a study of 12 HIV-infected men whose blood and semen samples were analyzed by Parel’s National Institute for Research in Reproductive Health (NIRRH).

The finding is significant, said scientists of NIRRH, as it negates the notion that an infected person can go slow on treatment or think of starting a family once the viral load in the bloodstream becomes undetectable.

The study clearly established that the type and behaviour of the HIV virus present in the bloodstream of an infected individual could be drastically different from the type and behaviour of the virus present in the same individual’s semen. In certain cases, it could look as if the individual is infected with two different types of virus altogether.

The pathbreaking HIV study, carried out by NIRRH in collaboration with the JJ Hospital’s medicine department, was recently published in the Journal of Medical Virology.

Principal investigator Dr A H Bandivadekar told TOI that the study proves that the virus could disappear from the blood stream due to anti-retroviral therapy but still be very much present in the semen. “This difference in the virus nature influences the transmission of HIV, the progression of the ailment, the virus’ response to the host defence and also treatment,” he added.

Further, Bandivadekar added that the study pointed out that sperm-associated virus too is a huge risk factor for HIV transmission and possibly for parent child transmission. “Therefore, assisted reproductive technology where sperm washing is used may not be termed as a completely safe procedure for maternal or fetal transmission of HIV,” he said.

The study further adds to the intriguing nature of the virus as it adds to the unpredictability, given its nature of constant mutation. In several of the individuals studied, the viral count in the blood differed vastly from the count in semen. For instance, while the blood plasma in one individual had 11,284 copies of the virus, the viral presence in his semen was around 5,432 copies. Also, in two individuals, the virus load in the blood had gone below detectable levels, but there were significant quantities of the virus present in the semen. Simply put, the virus in the blood and semen infect the same individual in different ways.

Head of JJ Hospital’s ART centre and one of the investigators, Dr Alka Deshpande, said the study also means that those on anti-retroviral medication should not think that it could keep the virus in both the compartments, blood and semen, under control. “It is now clear that there could be genetic differences in virus even if they are present in the same individual’s body,” she added. “It only means that whenever a vaccine or drug is created, the variant nature of the virus has to be kept in mind so that it can attack all compartments,” she added.

Wednesday, June 22, 2011

When Gladstone Institutes released evidence that Truvada, a one-a-day HIV pill, might prevent HIV in addition to treating it, the news sparked both excitement and skepticism.

The AIDS Healthcare Foundation (AHF), the largest HIV/AIDS medical provider in the country, came out against the use of Truvada for prevention, despite the fact that Gladstone’s Iniciativa Profilaxis Preexposicion (iPrEx) trial showed the drugs to be more than 90-percent effective in preventing HIV in those who took it daily.

Experts on the study sat down with Feast of Fun podcasters Fausto Fern?”s and Marc Felion at Center on Halsted June 15 to talk about what the study means and if Truvada could signal the end of the pandemic. Present were Dr. Robert Grant of Gladstone Institute, Keith Green, director of federal affairs at AIDS Foundation of Chicago, and a youth who participated in a similar study Green conducted in Chicago.

“In our wildest dreams, we did not think [Truvada] would be more than 90-percent effective in those who took it,” Grant told the audience.

The findings also astounded Green, who halted Project PrEPare, a similar Chicago study, because he didn’t want to continue administering placebos when he knew Truvada worked.

While the effectiveness of Truvada in preventing HIV is clear, the practicality of it remains uncertain. For one, Truvada is meant to be taken daily, which could pose a challenge to many not accustomed to the routine or whose lives don’t always allow for consistency, such as youth living on the street. Additionally, Truvada is not without side effects including nausea, although that tends to go away over prolonged use, said Grant.

One barrier in getting people to use Truvada is stigma, Grant said.

“These pills, in particular, have been the one thing that folks want to avoid,” he said, adding that fear surrounding HIV/AIDS contributes to fear around taking Truvada for prevention. “It strikes people as a misuse [of the drug].”

The drug could cost as much at $10,000 a year, an impossibly high price for people without insurance. In Illinois, the AIDS Drug Assistance Program (ADAP) which provides antiretrovirals to those who cannot afford them, is already cash-strapped. Truvada used for prevention could compete with Truvada treatments, creating a kind of Catch-22 for service providers who want to end the spread of HIV but also serve those who are positive already.

“We really have an ethical dilemma,” Green said.

Still, many insurance companies are interested in Truvada for prevention because even with the cost of the drug, prevention is at least half the cost of treatment.

Rico, the youth who participated in Green’s Chicago study on Truvada said that taking the drug made him “more considerate” of his body and protecting himself. He said that he had been hesitant to participate in the study but decided to sign up when he learned of the impact it could have on his community.

Grant and Green did acknowledge that iPrEx study had its shortcomings.

“I started to look at Dr. Grant’s work, and those people didn’t look like our people,” Green said, adding that a low number of youth and African Americans had participated. Grant agreed and noted that their efforts would seek the expertise of Chicago service providers whose work included a diversity of clients. Still he added, the drug seemed to work equally well among people of every race.

As for AHF’s critiques of using Truvada for prevention, neither Grant nor Green seemed to give them much weight.

“This is a large corporation, actually that has revenues above 300 million dollars a year, so well above my pay grade,” said Grant, who went on to say that he was not certain about why AHF was working to discredit the trial results.

Truvada is awaiting FDA approval before it can be marketed for HIV prevention. Grant said that Gilead, the company that makes Truvada, will likely be hesitant to market the drug for prevention and that it will be up to AIDS service providers to make the leap in making Truvada more accessible.

For some, that leap can’t come quickly enough.

“We either pay now or we pay forever,” Grant said. “We have a chance now to stop this epidemic.”

Tuesday, June 21, 2011

Some proteins can map aging process

Anabolic steroids, which are sometimes used to reverse loss of lean muscle tissue that is not only associated with disease such as HIV and cancer, but also with the normal aging process, can have unwanted side effects.

But a new research has shown that nine proteins, isolated from blood, alter with age and that the profile of some of these proteins can be reversed by testosterone treatment.

In a combined study, researchers from Boston University School of Medicine and University of Texas Medical Branch compared protein levels in serum samples from two groups of healthy men - young men aged 18-35 and older men aged 60-75.

Seven proteins, which were either growth factors (IGF-1, IL-7, IL-12p40, PDGFß), or were involved in immune response (ENA78, MIP-1ß, IP-10) and pro-collagen (PIIINP) were all reduced in older men. In contrast the monokine MIG, also involved in immune activity, was elevated.

Testosterone treatment increased lean muscle mass and levels of the appetite suppressing hormone leptin, for both groups of men. Testosterone also increased levels of PIIINP and IGF-1 in young men and the researchers saw a similar increase in a small group of older men.

Dr Monty Montano said, "The blood proteins we found that altered with healthy aging also have links to maintenance of muscle, such as IGF-1 and pro-collagen, or are involved in regulation of the immune system, possibly reducing T-cell and neutrophil responses with age. Additionally all of the proteins we found are involved with the signaling pathways controlled by AKT, NF?ß and TGFß which are known to be associated with aging."

"It is no simple matter to find a one size that fits all test for aging - our results suggest that there is a difference in response to anabolic steroids between young and older men, despite both groups increasing in muscle mass. It seems that testosterone replacement does not necessarily mean a restoration of full testosterone functionality for the older man,' added Montano.

Monday, June 20, 2011

Scientists using a powerful mathematical tool previously applied to the stock market have identified an Achilles heel in HIV that could be a prime target for AIDS vaccines or drugs.

The research adds weight to a provocative hypothesis—that an HIV vaccine should avoid a broadside attack and instead home in on a few targets. Indeed, there is a rare group of patients who naturally control HIV without medication, and these “elite controllers” most often assail the virus at precisely this vulnerable area.

“This is a wonderful piece of science, and it helps us understand why the elite controllers keep HIV under control,” said Nobel laureate David Baltimore. Bette Korber, an expert on HIV mutation at the Los Alamos National Laboratory, said the study added “an elegant analytical strategy” to HIV vaccine research.

“What would be very cool is if they could apply it to hepatitis C or other viruses that are huge pathogens—Ebola virus, Marburg virus,” said Mark Yeager, chair of the physiology department at the University of Virginia School of Medicine. “The hope would be there would be predictive power in this approach.” Drs. Baltimore, Korber and Yeager weren’t involved in the new research.

One of the most vexing problems in HIV research is the virus’s extreme mutability. But the researchers found that there are some HIV sectors, or groups of amino acids, that rarely make multiple mutations. Scientists generally believe that the virus needs to keep such regions intact. Targeting such sectors could trap HIV: If it mutated, it would disrupt its own internal machinery and sputter out. If it didn’t mutate, it would lie defenseless against a drug or vaccine attack.

The study was conducted at the Ragon Institute, a joint enterprise of Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University. The institute was founded in 2009 to convene diverse groups of scientists to work on HIV/AIDS and other diseases.

Two of the study’s lead authors aren’t biologists. Arup Chakraborty is a professor of chemistry and chemical engineering at MIT, though he has worked on immunology, and Vincent Dahirel is an assistant professor of chemistry at the Université Pierre et Marie Curie in Paris. They collaborated with Bruce Walker, a longtime HIV researcher who directs the Ragon Institute. Their work was published Monday in the Proceedings of the National Academy of Sciences.

To find the vulnerable sectors in HIV, Drs. Chakraborty and Dahirel reached back to a statistical method called random matrix theory, which has also been used to analyze the behavior of stocks. While stock market sectors are already well defined, the Ragon researchers didn’t necessarily know what viral sectors they were looking for. Moreover, they wanted to take a fresh look at the virus.

So they defined the sectors purely mathematically, using random matrix theory to sift through most of HIV’s genetic code for correlated mutations, without reference to previously known functions or structures of HIV. The segment that could tolerate the fewest multiple mutations was dubbed sector 3 on an HIV protein known as Gag.

In an interview with WSJ’s Mark Schoofs, NIAID director Dr. Anthony Fauci reflects on his thirty years spent fighting AIDS, and how he believes science is at a turning point where it has the potential to dramatically shrink the size of the AIDS epidemic across the globe.

Previous research by Dr. Yeager and others had shown that the capsid, or internal shell, of the virus has a honeycomb structure. Part of sector 3, it turns out, helps form the edges of the honeycomb. If the honeycomb suffered too many mutations, it wouldn’t interlock, and the capsid would collapse.

For years, Dr. Walker had studied rare patients, about one in 300, who control HIV without taking drugs. He went back to see what part of the virus these “elite controllers” were attacking with their main immune-system assault. The most common target was sector 3.

Dr. Walker’s team found that even immune systems that fail to control HIV often attack sector 3, but they tend to devote only a fraction of their resources against it, while wasting their main assault on parts of the virus that easily mutate to evade the attack. That suggested what the study’s authors consider the paper’s most important hypothesis: A vaccine shouldn’t elicit a scattershot attack, but surgical strikes against sector 3 and similarly low-mutating regions of HIV.

“The hypothesis remains to be tested,” said Dan Barouch, a Harvard professor of medicine and a colleague at the Ragon institute. He is planning to do just that, with monkeys. Others, such as Oxford professor Sir Andrew McMichael, are also testing it.

The Ragon team’s research focused on one arm of the immune system—the so-called killer T-cells that attack other cells HIV has already infected. Many scientists believe a successful HIV vaccine will also require antibodies that attack a free-floating virus. Dr. Chakraborty is teaming up with Dennis Burton, an HIV antibody expert at the Scripps Research Institute in La Jolla, Calif., to apply random matrix theory to central problems in antibody-based vaccines.

Friday, June 17, 2011

HIV and Aging — A Report on NYC

The U.S. Centers for Disease Control and Prevention (CDC) estimates that more than a million adults and adolescents are living with HIV in the United States. New York City, the epicenter of HIV, has the largest amount of diagnosed persons in the United States. The HIV/AIDS time line began in July 1981, when The New York Times reported an outbreak of a rare form of cancer among gay men in New York City. This ‘cancer’ was identified as Kaposi’s sarcoma, a disease that later became known as HIV/AIDS. Emergency rooms in NYC began to see more and more seemingly healthy young men with flu-like symptoms and a rare form of pneumonia. This began what today is one of the biggest health concerns in modern history.

According to a study made by AIDS Community Research Initiative of America (ACRIA), almost 27 percent of all people living with AIDS in the United States are over 50 years old. In New York City this number goes up to 35 percent. Thanks to research and the introduction of highly effective antiretroviral therapy (HAART), mortality rates and increased life expectancy for people living with HIV and AIDS is higher than ever. Soon we will see a large number of senior citizens with HIV and AIDS. There are three groups of older adults with HIV, the newly infected, the newly diagnosed and the aging individual/longtime survivor. These groups have different but overlapping medical and psycho-social needs.

Research has demonstrated that older adults and seniors with HIV or AIDS face multiple forms of discrimination. Not only do they face the everyday discrimination everyone with HIV and AIDS confronts, but they also have to deal with discrimination related to their age and their health care. For example, a lot of physicians do not perceive older adults to be at risk for HIV infection; and therefore they are less likely to be tested for the virus. In fact, a study of people between the age of 60 and 79 years old who had died in a long-term healthcare facility found that five percent were HIV antibody positive although none had been diagnosed with HIV.

Seniors in the context of HIV and AIDS have somewhat become invisible. They are rarely targeted in HIV prevention campaigns and therefore, they may not realize that their behaviors can put them at risk for HIV infection.

Some two out of three HIV infected older adults in NYC suffers from depression. Depression for older people can be particularly destructive. Caregivers often fail to recognize the symptoms of depression in the elderly; it is often seen as a characteristic of aging rather than an illness. Loneliness and HIV related stigma are two major reasons for the high numbers of depression among HIV positive older adults.

Even though nations and individuals have made progress in treating this condition, HIV and Aids is still highly stigmatized. A lot of older adults feel ashamed and guilty about their condition and don’t feel comfortable telling their family and friends. We can speculate that HIV and AIDS are often related to sex and drugs which may make some people uncomfortable and they would prefer not being associated with it. The study made by ACRIA showed that fewer than half told all their family members and only one-third told their friends that they were HIV positive. Older adults and seniors grew up during a time when discussions about sexuality were considered improper or vulgar; one simply did not talk about sex in the same way that we do today. Some individuals who chose to tell friends and family felt that the ignorance about how HIV is spread still is a problem. After they revealed their illness some felt that people around them would for instance stop touching them and reject them. For example, one person said that after revealing his illness to his family, they would give him plastic plates, knives and forks. Some of these problems even occur within health clinics.

What can be Done?
It is essential that researchers start conducting more research targeting the older population. Many people with HIV infection are now living long enough to experience HIV as a chronic illness. More research is needed on HIV/AIDS and aging, so that we can understand the interaction and overlapping with age-related symptoms and HIV. We need to change the knowledge level and attitudes towards HIV and aging. To prevent new infected cases, we need to start campaigns that specifically targets older adults. Physicians must challenge the myths and start asking older patients about their sexual activity. Doctors must not overlook the possibility that older people are at risk for HIV. If we can do this, I think we come a long way.

RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR kinases on HIV-1 expression and RNA processing was examined.

Results: Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus.

Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production.

Conclusions: Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

We previously reported that two conservative NC mutations, His23Cys and His44Cys, cause premature reverse transcription such that mutant virions contain approximately 1,000-fold more DNA than wild-type virus, and are replication defective. In addition, both mutants show a specific defect in integration after infection.

Results: In the present study we investigated whether blocking premature reverse transcription would relieve the infectivity defects, which we successfully performed by transfecting proviral plasmids into cells cultured in the presence of high levels of reverse transcriptase inhibitors.

After subsequent removal of the inhibitors, the resulting viruses showed no significant difference in single-round infective titercompared to viruses where premature reverse transcription did occur; there was no rescue of the infectivity defects in the NC mutants upon reverse transcriptase inhibitor treatment. Surprisingly, time-course endogenous reverse transcription assays demonstrated that the kinetics for both the NC mutants were essentially identical to wild-type when premature reverse transcription was blocked.

In contrast, after infection of CD4+ HeLa cells, it was observed that while the prevention of premature reverse transcription in the NC mutants resulted in lower quantities of initial reverse transcripts, the kinetics of reverse transcription were not restored to that of untreated wild-type HIV-1.

Conclusions: Premature reverse transcription is not the cause of the replication defect but is an independent side-effect of the NC mutations.

Although treatment experienced HIV-positive men and women had slightly greater gains in trunk fat after switching to a new regimen containing Prezista (darunavir), they also reported increased satisfaction with their bodies. These data were published in the July issue of AIDS Patient Care and STDs.

Of all of the side effects to HIV medication, body shape changes—both the loss of body fat in the face and limbs and gains of body fat in the trunk and other areas—are among the most distressing to people living with HIV. In fact, body shape changes have been identified as an independent cause of adherence problems in people taking antiretroviral (ARV) therapy.

Though body shape changes are less of a risk with the drugs that are more commonly used today, they do still occur in some people. This is particularly true in people who are heavily treatment experienced, who must sometimes combine the newer ARV drugs with older medication.

To determine the impact of Prezista on body shape changes and people’s perception of their bodies, Judith Currier, MD, from the University of California in Los Angeles, and her colleagues examined data from a large study of Norvir (ritonavir)–boosted Prezista in a diverse group of treatment-experienced people. The study, called GRACE, was the first that was specifically designed to compare the safety and effectiveness of an ARV medication between men and women and between white and black study participants.

In this particular analysis, Currier and her colleagues measured changes in trunk over time and also surveyed the GRACE study participants about their perceptions of their bodies and their satisfaction with their appearance. In all, 287 HIV-positive women and 142 HIV-positive men were examined for this analysis, all of whom received at least one dose of Prezista. In general, women in the study had less severe HIV disease progression at the study’s start.

Currier’s team found that although the participants gained weight and their waist size increased during the course of the study—by 2.5 centimeters (cm) in women and 1.3 cm in men—the participants nevertheless reported greater body satisfaction by the end of the study. In women, those who reported being either “satisfied” or “very satisfied” with their body appearance increased from 42 percent to 58 percent over the course of the study. In men, those “satisfied” or “very satisfied” increased from 56 percent to 63 percent.

Given the discrepancy between people’s actual body shape changes and their reported satisfaction with their bodies, the authors are calling for further study. First, the authors suggest that additional exploration is needed to better understand the reasons behind the body shape changes. Second, they urge that we need a better and more thorough understanding about how people perceive their bodies and how this may affect adherence.

Better Assessment Of Drug Resistance May Improve Treatment Of People With HIVBy April Clayton and Courtney McQueen

Results from a recent small Spanish study indicate that a more sensitive technique for detecting drug resistance, called deep sequencing, more accurately identified drug resistance in HIV-positive individuals who had previously been treated with antiretrovirals and were suffering from drug failure.

“Our study suggests that more sensitive genotypic HIV drug resistance assays, such as deep HIV sequencing, may help clinicians design antiretroviral treatment combinations better suited for [patients] infected with multidrug-resistant viruses,” said Dr. Roger Paredes, a key investigator of the study, in correspondence with The AIDS Beacon.

“Deep sequencing may help [clinicians] choose more effective drugs as well as avoid antiretrovirals to which, in fact, the virus is resistant,” he added.

Drug resistance is one of the main causes of antiretroviral drug failure. HIV-positive individuals are considered resistant to an anti-HIV drug if their viral load (amount of HIV in the blood) does not remain low after drug therapy or testing confirms the presence of an HIV strain that is resistant to one or more classes of antiretrovirals.

Resistance testing examines the genes of the HIV in a person’s blood to detect whether the virus has mutations that make it resistant to particular drugs. Previous studies have indicated that even low levels of drug-resistant HIV increase the chances of treatment failure, although those studies have primarily involved previously untreated people with HIV (see related AIDS Beacon news)

The authors of this study investigated whether an enhanced form of resistance testing, known as deep sequencing, could provide better assessments of drug resistance in heavily pre-treated HIV patients when compared to the more traditional form of resistance testing, called population sequencing.

Deep sequencing detects the same mutations as population sequencing but is more sensitive, so it can detect mutations present in 1 percent or more of the HIV circulating in a person’s blood. Population sequencing can usually only detect mutations present in 15 percent or more of the HIV.

Seven HIV-positive individuals participated in the study. Participants had taken a median of 15 antiretroviral drugs for a median of 13 years. The average age of the participants was 44, and five of the seven were male.

All participants had shown resistance to the three main classes of antiretrovirals: nucleoside-reverse transcriptase inhibitors (NRTIs), protease inhibitors, and non-nucleoside reverse transcriptase inhibitors. In addition, all participants had failed salvage therapy with at least one of the following: Prezista (darunavir), Aptivus (tipranavir), Intelence (etravirine), or Isentress (raltegravir).

Results showed that deep sequencing detected all of the drug resistant mutations found by population sequencing, plus additional resistance mutations in six of the seven participants.

In particular, deep sequencing improved the assessment of resistance to Intelence, showing higher risk of resistance in two patients with signs of failing Intelence-based therapy. The technique also slightly modified assessments of HIV resistance against Sustiva (efavirenz), Crixivan (indinavir), and NRTIs in various participants to indicate higher risks of resistance, compared to the population sequencing.

The two methods identified the same participants as having drug resistance to Aptivus and Isentress, and the deep sequencing confirmed that four of five participants who had failed Isentress-based antiretroviral therapy did not show resistance to the drug and could potentially take it again.

Dr. Paredes stated that the researchers are currently conducting a larger study to investigate whether the use of deep sequencing can lead to improved treatment outcomes for treatment-experienced patients starting salvage therapy with Norvir (ritonavir)-boosted protease inhibitors, Intelence, or Isentress.

Thursday, June 16, 2011

A molecule extracted from a marine micro-organism, found off the coast of Rameshwaram, could potentially be the next biggest development in treating TB and HIV, claimed researchers here on Wednesday.

Offering new hope to those living with HIV as well as TB patients, a group of scientists from the Tuberculosis Research Centre (TRC), IIT-Madras and Periyar University claim to have extracted the molecule, Transitmycin, from the marine micro-organism, ‘Streptomyces sp’, that was isolated from a soil sample collected from the coral reef off the coast of Rameshwaram. The brominated and pigmented antibiotic has been found to be active against both TB and HIV, said researchers.

“Transitmycin inhibited drug sensitive, multidrug resistant (MDR) and XDR Mycobacterium tuberculosis strains as well as bacterial pathogens,” said Dr Vanaja Kumar, principal investigator and head of the department of bacteriology at the TRC. It was also found to be active against latent bacilli, said the researchers. Enthusing them further, the compound was found to inhibit two most widely prevalent clades of HIV-1, the subtypes B & C.

Experts said the latter subtype was most prevalent in India and parts of the African continent, reportedly responsible for the worst epidemics and around half of all infections.

Importantly, this compound is found to be effective against both Mycobacterium and HIV, a unique feature that enables the treatment of patients who have been infected with both these pathogens unlike the existing medicines that cannot be administered simultaneously as they counteract, said the scientists.

Preclinical research, including animal studies, are to be taken up prior to testing this compound in human clinical trials, they said, adding that it would be ready in 10 years if the plan fell in place.

Tuesday, June 14, 2011

Researchers Find High Rates Of Heart Disease And High Cholesterol In People With HIVBy April Clayton

Results from a recent Brazilian study indicate that a high proportion of HIV-positive individuals on antiretroviral therapy have abnormal cholesterol and triglyceride levels. Additionally, almost 40 percent of HIV-positive individuals in the study were at an increased risk for heart disease.

Based on their results, the authors of the study suggested that intervention programs be implemented to reduce the risk of heart disease in people with HIV taking antiretrovirals.

Although antiretroviral therapy slows the progression of HIV and has helped prevent HIV-related deaths, it can lead to side effects such as weight gain, high cholesterol and triglyceride levels, and insulin resistance or pre-diabetes.

Results of several previous studies have indicated that the use of protease inhibitors in particular is associated with high levels of cholesterol in people with HIV (see related AIDS Beacon news).

These side effects can lead to serious health problems, such as heart disease and diabetes.

In this study, researchers investigated the rates of high cholesterol and triglyceride levels and risk for cardiovascular disease in 113 people with HIV who were on antiretroviral therapy. The average age of study participants was 39 years old and 68 percent were male.

Results showed that two-thirds of study participants (67 percent) had problems with their cholesterol or triglyceride levels. Almost 54 percent of participants had low levels of “good” cholesterol and 36 percent had high levels of triglycerides; 27 percent had borderline-high or high cholesterol.

Results also showed that participants taking a protease inhibitor-based regimen had a more than five-fold higher risk for abnormal cholesterol or triglyceride levels than patients on antiretroviral therapy without protease inhibitors.

In addition, almost 40 percent of individuals with HIV had changes in body fat distribution, particularly body fat accumulation.

The researchers also assessed the risk for heart disease in 97 participants. Results showed that 37 percent of the HIV-positive men and 40 percent of the HIV-positive women had a high risk for heart disease.

The researchers found no link between age, length of HIV infection, gender, viral load (amount of HIV in the blood), or CD4 (white blood cell) count and risk of abnormal cholesterol or triglyceride levels.

For more information, please see the study in the Brazilian Journal of Infectious Diseases (abstract).

There is evidence of some groups of gay men knowing, from the late 1990s onwards, that people with an undetectable HIV viral load were much less infectious, and were using this knowledge in sexual decision-making. Public discussion of this became much more high profile after a paper was issued by the Swiss Federal Commission for HIV/AIDS in January 2008.

The authors of the Swiss Statement have since said that they were surprised at the amount of attention their paper got and the global discussion it set off. It was intended purely as an incountry guideline directed at doctors and, significantly, at legal professionals. Much of the motivation for the statement lay in the fact that Switzerland had prosecuted and convicted a number of HIV+ people for exposing partners to HIV, and the doctors wanted there to be a statement saying that HIV+ people posed no risk to their partners if they were undetectable on stable antiretroviral therapy. They stated that unprotected sex between a positive person on antiretroviral treatment, and without an STI, and an HIV-negative person did not comply with the criteria for an “attempt at propagation of a dangerous disease” in the Swiss penal code nor for “an attempt to engender grievous bodily harm”.

Although the statement purely concerns the position of individuals and was not connected with the mathematical-modelling studies that were starting to be issued which looked at the possibility of using viral control as a prevention measure, it was significant because it transformed the discussion around viral undetectability and infectiousness from one in which using viral load status to inform sexual-risk decisions was seen as dangerous, and a rationalisation for having unprotected sex, to one in which it became possible to talk about its legitimate use as a prevention measure.

Nonetheless, the statement caused widespread concern amongst some prevention and public health advocates who felt it was based on weak evidence in some areas and risked undermining people’s efforts to maintain and promote condom-based safer sex.

The statement said that people with HIV are not sexually infectious (“ne transmettent pas le VIH par voie sexuelle”), as long as the following conditions are met:

The HIV+ individual takes antiretroviral therapy consistently and as prescribed and is regularly followed by his/her doctor.

Viral load is ‘undetectable’ and has been so for at least six months.

The HIV+ individual does not have any STIs.

The original statement made no distinction between vaginal and anal sex, though all the evidence the writers cited in support of the statement concerned heterosexual transmission, such as the Rakai study, and they have since said that the statement only covered heterosexual transmission.

The statement had five co-authors, four of them Switzerland’s foremost HIV experts: Professor Pietro Vernazza, of the Cantonal Hospital in St Gallen, and President of the Swiss Federal Commission for HIV/AIDS; Professor Bernard Hirschel from Geneva University Hospital; Dr Enos Bernasconi of the Lugano Regional Hospital; and Dr Markus Flepp, President of the Swiss Federal Office of Public Health’s Sub-committee on the clinical and therapeutic aspects of HIV/ AIDS. Significantly, its fifth author was a community activist, François Wasserfallen of the European AIDS Treatment Group, thus ensuring that community ‘buy-in’ for the statement was present from the start.

The Commission states that an HIV+ person in a stable relationship with an HIV-negative partner, who follows their antiretroviral treatment consistently and as prescribed and who does not have an STI, is “not putting their partner at risk of transmission by sexual contact”.

However, they emphasise that, “Couples must understand that adherence will become omnipresent in their relationship when they decide not to use protection, and due to the importance of STIs, rules must be defined for sexual contacts outside of relationship.”

They add that heterosexual women will have to consider eventual interactions between contraceptives and antiretrovirals before considering stopping using condoms. They also say that insemination[ix] via sperm washing is no longer indicated when “antiretroviral treatment is efficient.”

The Commission goes on to say that it “is not for the time being, considering recommendations that HIV+ individuals start treatment purely for preventative measures.” Aside from the cost involved, they argue, it cannot be certain that HIV+ people would be sufficiently motivated to follow, and apply to the letter, antiretroviral treatment on a long-term basis without medical indications. They note that poor adherence is likely to facilitate the development of resistance, and that, therefore, antiretroviral therapy as prevention is indicated only in “exceptional circumstances for extremely motivated patients”.

The Commission also says that their statement should not change prevention strategies currently taking place in Switzerland. With the exception of stable HIV+ couples where HIV-positivity and the efficacy of antiretroviral therapy can be established, measures to protect oneself must be followed at all times. “People who are not in a stable relationship must protect themselves,” they note, “as they would not be able to verify whether their partner is positive or on efficient antiretroviral therapy.”

At a meeting in Mexico City in August 2008, Pietro Vernazza clarified some aspects of the statement. “We never thought of it as a statement that was to be delivered worldwide,” he said, but rather “it was meant only to be delivered to Swiss physicians to help them discuss sexual risk-taking with their patients and their steady partners.” He regretted the “ne transmettent pas” in the statement’s title and said that this absolute phrasing was ‘misleading’ in that it appeared to rule out the possibility of any residual risk.

“We also made it clear that the only person who can assess perfect adherence and regular check-ups would be a steady partner, and that it should only be the informed [HIV-negative] partner who could assess the risks for themselves.” The statement, he said, was “good news for a small number of people, but [for everyone else] prevention messages remain unchanged”.

Nonetheless, he defended the applicability of the statement at least to heterosexual couples in the light of subsequent research, including the Wilson paper in The Lancet, which said that gay male couples where the HIV+ partner was on treatment could reduce their transmission risk to virtually zero if they also used condoms, and said the estimated residual risk to heterosexual couples where the HIV+ partner was on treatment was of the same order as other possible, but unlikely, hazards such as the risk of dying in an air crash or avalanche.

Monday, June 13, 2011

With Koronis, Is A Cure For HIV On The Horizon?Kerry A. Dolan

Here’s a compelling thought: All the HIV drugs currently on the market work by suppressing some form of the virus and its ability to replicate itself. What if you created a drug that did the opposite–one that uses the replication process to get the virus to mutate more often, something that makes the HIV virus eventually weaken and collapse?

Scientists at Koronis Pharmaceuticals, a small private biotech company in Seattle, have a drug candidate that does just that. It’s been tested in 80 people who have HIV and for whom existing drugs were no longer effective. Results from the Phase 2-A trial, released in January, showed that Koronis’ experimental drug does increase the frequency of mutations in the HIV genome.

More trials have to be done to determine if the Koronis drug can essentially take down the HIV virus, but at least one analyst believes it could be a game changer. Katherine Xu, a biotech analyst for William Blair, said in a report earlier this year that the Koronis drug has “huge potential for disruption.” One scenario she paints: that the Koronis drug be given in combination with an existing drug like Atripla and “after a year or so, the viruses could be mutated out of existence and the patients could achieve a cure,” Xu wrote in a report for Wedbush Securities, where she worked until recently. “If it were to be successful, it would be great news for the field,” Xu told me last week in a phone interview.

Scientists at Koronis have been able to eradicate HIV in a petri dish. Doing so in humans is likely to be much more difficult, but worth a try. Traditional HIV drugs attempt to block viral replication. Koronis CEO Donald Elmer explains that the Koronis drug uses the viral replication process to induce additional mutations in the HIV genome by mismatch base pairing. “These additional mutations progressively debilitate the virus, which ultimately results in collapse of the viral population,” he says.

This month marks 30 years since the virus now called HIV made its first horrific emergence among gay men. Incredible progress has been made in the decades since, but almost all of that is evidenced in the U.S. and Europe. Of the 33 million people living with HIV, 25 million are not currently being treated; 90% of the $14 billion a year spent on treating HIV is focused in North America and Europe.

“Outside the U.S., HIV is still a pandemic,” says Koronis CEO Elmer, who says that treating HIV is complicated and requires regular monitoring –something that just isn’t happening in poor countries. Thus the urgent need for a new kind of treatment. A lurking concern –and another reason to pursue new kinds of drugs — is the rise of drug-resistant HIV.

The next step for Koronis is to come up with $15 million to $20 million to perform a clinical trial that would combine its drug candidate with an approved drug that is currently used for HIV treatment. The company has raised $43 million since it was founded in 2002 but is in need of outside cash. It’s in discussions with the six big companies that operate in the HIV sector – Gilead (GILD), Bristol-Myers Squibb (BMY), Abbott Laboratories (ABT), Viiv (which is a joint venture between Pfizer and GlaxoSmithKline), Johnson & Johnson and Merck – but is pursuing other avenues as well –including a possible partnership with a non-U.S. company. It’s open to investment from deep-pocketed individuals who want to help further HIV drug development.

Finding a cure for HIV has been a holy grail for scientists in the field. It’s way too early to say for sure that the Koronis drug is the route to that cure. But until it undergoes further tests, it’s too early to rule it out as well.

Sunday, June 12, 2011

SAN FRANCISCO (AP) — Having survived the first and worst years of the AIDS epidemic, when he was losing three friends to the disease in a day and undergoing every primitive, toxic treatment that then existed, Peter Greene is grateful to be alive.

But a quarter-century after his own diagnosis, the former Mr. Gay Colorado, now 56, wrestles with vision impairment, bone density loss and other debilitating health problems he once assumed he wouldn’t grow old enough to see.

“I survived all the big things, but now there is a new host of things. Liver problems. Kidney disease. It’s like you are a 50-year-old in an 80-year-old body,” Greene, a San Francisco travel agent, said. “I’m just afraid that this is not, regardless of what my non-HIV positive friends say, the typical aging process.”

Even when AIDS still was almost always fatal, researchers predicted that people infected with HIV would be more prone to the cancers, neurological disorders and heart conditions that typically afflict the elderly. Thirty years after the first diagnoses, doctors are seeing these and other unanticipated signs of premature or “accelerated” aging in some long-term survivors.

Government-funded scientists are working to tease apart whether the memory loss, arthritis, renal failure and high blood pressure showing up in patients in their 40s and 50s are consequences of HIV, the drugs used to treat it or a cruel combination of both. With people over 50 expected to make up a majority of U.S. residents infected with the virus by 2015, there’s some urgency to unraveling the “complex treatment challenges” HIV poses to older Americans, according to the National Institutes of Health.

“In those with long-term HIV infection, the persistent activation of immune cells by the virus likely increases the susceptibility of these individuals to inflammation-induced diseases and diminishes their capacity to fight certain diseases,” the federal health agency’s chiefs of infectious diseases, aging and AIDS research wrote, summing up the current state of knowledge on last September’s National HIV/AIDS and Aging Awareness Day. “Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver and lung disease, as well as many cancers not associated directly with HIV infection.”

In San Francisco, where already more than half of the 9,734 AIDS cases are in people 50 and over, University of California, San Francisco AIDS specialists are collaborating with geriatricians, pharmacists and nutritionists to develop treatment guidelines designed to help veterans of the disease cope with getting frail a decade or two ahead of schedule and to remain independent for as long as possible.

“Wouldn’t it be helpful to be able to say, are you at high risk, low risk or moderate risk for progressing to dependency in the next five, the next 10 years, being less mobile, less able to be functional in the workplace. Are you going to be safe in your home, are you going to remember to take all those medications? How are they going to interact?” explained Dr. Malcolm John, who directs UCSF’s HIV clinic. “All those questions need to be brought into the HIV field at a younger age.”

Research so far suggests that HIV is not directly causing conditions that mimic old age, but hastens patients toward ailments to which they may have been genetically or environmentally predisposed. Plus, their immune systems are being weakened over time even when they are being successfully treated for AIDS, John said.

“That’s probably true for a lot of these things. We aren’t saying HIV’s starting the problem, but it’s added fuel on top,” he said.

Stokes, a patient of John’s who goes by only his last name, is a prime example. At 53, HIV-positive since 1985 and in substance abuse recovery for the last 11 years, he says he is happier than he ever has been. Yet the number of ailments for which he is being treated would be more commonly found in someone 30 years his senior: a condition called Ramsay Hunt syndrome that causes facial paralysis, a rare cartilage disorder for which he has undergone four ear surgeries, bone death in the hip and shoulder, deterioration of his heart muscle, osteoporosis and memory loss.

A specialist recently diagnosed a Kaposi’s sarcoma spot on Stokes’ ankle. Although the cancer is not life-threatening, the sight of young men disfigured by KS lesions was a harbinger of the early AIDS crisis, and its presence on his own body is unsettling.

At his therapy group for men with HIV, aging “comes up frequently,” he said. “I say, ‘Just think what we have come through to have a life today.’“ At the same time, he acknowledges sometimes feeling self-conscious about his physical appearance and worries if “people are not attracted to me and unwilling to go the length of what it means to be with me, no matter how brilliant my mind or my zest for life.”

Loneliness, financial worries and concerns about who will care for them and where can weigh on long-term AIDS survivors in the same way as all adults living in a society that values youth, Charles Emlet, a social work professor at the University of Washington, Tacoma, said.

As they get older and sicker, many feel “doubly stigmatized,” he said. Some people who have lived with the virus for a long time have been getting by on private disability benefits that will run out when they turn 65, forcing them to move to less expensive locations or to consider turning to estranged family members. Like soldiers from a distant war, many lost partners and their closest friends to AIDS.

Such emotional side effects, combined with the physical toll of managing chronic health problems, put older AIDS patients at risk for depression. At the same time, Emlet has uncovered evidence that a majority of long-term survivors also share another trait that typically comes with advanced age: that is, the ability to draw strength from their difficult experiences.

“The older adults I’ve interviewed, many of them talk about how much it means to them to give back, to do something positive with the years they never expected to have,” he said.

Peter Greene can relate to that. At times, like the days he is so exhausted he can’t get out of bed or the pain from his multiple maladies is too intense, he asks himself “the Carrie Bradshaw question—are we really lucky to still be alive?”

As frightening and uncertain as this phase of AIDS is, he thinks he knows the answer.

“I’ve tried to make the time I have count, and really, now that I have the body of an 80-year-old, I probably have the wisdom of an 80-year-old as well, which counts for a lot,” Greene said. “Everything becomes clear at the end of your life and in some ways, thinking you’ve been dying all these years, you get moments of clarity that I don’t think everyone gets.”